{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:06:43Z","timestamp":1790978803928,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,3,5]],"date-time":"2003-03-05T00:00:00Z","timestamp":1046822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Anat. Rec."],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypohidrotic (anhidrotic) ectodermal dysplasia (HED), the most common of the \u223c150 described ectodermal dysplasias, is a disorder characterized by abnormal hair, teeth, sweat glands, and salivary glands. Mutations in the <jats:italic>EDA<\/jats:italic> (<jats:italic>ectodysplasin\u2010A<\/jats:italic>) and <jats:italic>EDAR<\/jats:italic> (<jats:italic>ectodysplasin\u2010A receptor<\/jats:italic>) genes are responsible for X\u2010linked and autosomal HED, respectively. Abnormal phenotypes similar to HED are seen in <jats:italic>Tabby<\/jats:italic> (<jats:italic>Eda<\/jats:italic><jats:sup><jats:italic>Ta<\/jats:italic><\/jats:sup>) and <jats:italic>downless<\/jats:italic> (<jats:italic>Edar<\/jats:italic><jats:sup><jats:italic>dl<\/jats:italic><\/jats:sup>) mutant mice. Although recent studies have focused on the role of Eda\/Edar signaling during hair and tooth development, very little is known about its role during embryonic submandibular salivary gland (SMG) development. To this end, we analyzed the SMG phenotypes in <jats:italic>Tabby<\/jats:italic> (<jats:italic>Ta<\/jats:italic>) and <jats:italic>downless<\/jats:italic> (<jats:italic>dl<\/jats:italic>) mutant mice and determined that <jats:italic>Ta<\/jats:italic> SMGs are hypoplastic, whereas <jats:italic>dl<\/jats:italic> SMGs are severely dysplastic. The absence of SMG ducts and acini in <jats:italic>dl<\/jats:italic> SMGs suggests that Eda\/Edar signaling is essential for lumina formation and glandular histodifferentiation. Our localization of Eda and Edar proteins at sites of lumen and acini formation supports this conclusion. Moreover, the presence of SMGs in both <jats:italic>Ta<\/jats:italic> and <jats:italic>dl<\/jats:italic> mutant mice, as well as the absence of immunodetectable Eda and Edar protein in Initial Bud and Early Pseudoglandular stage SMGs, indicate that Eda\/Edar\u2010mediated signaling is important for branching morphogenesis and histodifferentiation, but not for initial gland formation. To initially delineate the morphoregulatory role of Eda\/Edar\u2010mediated signaling during embryonic SMG development, we cultured embryonic day 14 SMGs with enhanced or abrogated Eda\/Edar signaling. Eda supplementation induced a significant increase in SMG branching, and enhanced activation of NF\u2010\u03baB. Abrogating Eda\/Edar signaling by adding the soluble form of Edar to bind endogenous ligand in embryonic SMGs results in a significant dose\u2010dependent decrease in branching morphogenesis. Taken together, our results suggest that the Eda\/Edar\/NF\u2010\u03baB pathway exerts its effect on SMG epithelial cell proliferation, lumina formation, and histodifferentiation. Anat Rec Part A 271A:322\u2013331, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ar.a.10045","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T17:47:43Z","timestamp":1048009663000},"page":"322-331","source":"Crossref","is-referenced-by-count":54,"title":["Ectodysplasin receptor\u2010mediated signaling is essential for embryonic submandibular salivary gland development"],"prefix":"10.1002","volume":"271A","author":[{"given":"Tina","family":"Jaskoll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Min","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Trump","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Melnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,3,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1305"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.11.1661"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092070104"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199705000-00010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.62.10.989"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.61.5.559"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1242\/dev.127.3.483","article-title":"An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal\u2010epithelial signaling during mouse organogenesis","volume":"127","author":"De Moerlooze L","year":"2000","journal-title":"Development"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/85837"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.9.953"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.9.1581"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.11.2079"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.9.1589"},{"key":"e_1_2_8_14_1","first-page":"92","article-title":"The EGF system in fetal development","volume":"36","author":"Gresik EW","year":"1998","journal-title":"Eur J Morphol"},{"key":"e_1_2_8_15_1","first-page":"137","article-title":"Genes and genotypes affecting the teeth of the mouse","volume":"14","author":"Gruneberg H","year":"1965","journal-title":"J Embryol Exp Morphol"},{"key":"e_1_2_8_16_1","first-page":"1","article-title":"The glandular aspect of the tabby syndrome in the mouse","volume":"25","author":"Gruneberg H","year":"1971","journal-title":"J Embryol Exp Morphol"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.1994.00567.x"},{"key":"e_1_2_8_18_1","first-page":"570","volume-title":"Antibodies: a laboratory manual","author":"Harlow E","year":"1988"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/11943"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/414913a"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00062-8"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(19991101)256:3<252::AID-AR5>3.0.CO;2-6"},{"key":"e_1_2_8_23_1","unstructured":"JaskollT MelnickM.2002. 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